Brain regeneration: Crayfish turn blood into neurons

Think crayfish and you probably think supper, perhaps with mayo on the side. You probably don’t think of their brains. Admittedly, crayfish aren’t known for their grey matter, but that might be about to change&colon; they can grow new brain cells from blood.

Humans can make new neurons, but only from specialised stem cells. Crayfish, meanwhile, can convert blood to neurons that resupply their eyestalks and smell circuits. Although it’s a long way from crayfish to humans, the discovery may one day help us to regenerate our own brain cells.

Olfactory nerves are continuously exposed to damage and so naturally regenerate in many animals, from flies to humans, and crustaceans too. It makes sense that crayfish have a way to replenish these nerves. To do so, they utilise what amounts to a “nursery” for baby neurons, a little clump at the base of the brain called the niche.

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In crayfish, blood cells are attracted to the niche. On any given day, there are a hundred or so cells in this area. Each cell will split into two daughter cells, precursors to full neurons, both of which migrate out of the niche. Those that are destined to be part of the olfactory system head to two clumps of nerves in the brain called clusters 9 and 10. It’s there that the final stage of producing new smell neurons is completed.

Without resupply, the niche’s stash of precursor neurons should gradually dry up, but does not happen, suggesting the existence of a secret source of them. Barbara Beltz of Wellesley College in Massachusetts knew from Petri dish experiments that crayfish blood cells – haemocytes – are attracted to the niche.

Remarkable migration

To test what happens to the blood, she used a chemical called astakine 1, which controls the production of haemocytes, to tweak the number that were coursing around live animals. This, she found, also changed the number of cells in the niche. And more haemocytes meant more baby neurons.

Beltz’s team then extracted haemocytes from “donor” crayfish, labelled them with a DNA dye and pumped them back into different “receptor” crayfish. Three days after transfusion, the label showed up in cells in the niche. Seven days later it was at the base of clusters 9 and 10. And seven weeks after transfusion the labelled cells were producing neurotransmitters, the chemicals that neurons use to communicate with each other.

Exactly how the blood cells are reprogrammed to become brain cells is a mystery, but understanding the mechanism could help us devise new therapies to reprogram human cells, says Beltz.

“The study is very thorough,” says Chris Mason of University College London. It shows that two cell systems that are normally thought to be completely separate – cells that make blood and cells that make neurons – can cross over.

How to regenerate neurons is a key question for those studying neurodegenerative conditions like Parkinson’s disease. Several groups try to persuade stem cells to turn into neurons, and Beltz points out that the precursor neurons in crayfish are similar to human stem cells with the exception that the human versions self-regenerate. In humans, after a stem cell splits in two, only one of the daughter cells migrates away and differentiates into a specialised cell, leaving one behind to produce more daughter cells.

Start simple

“It is a very long way from crayfish to humans,” says Anthony Windebank of the Mayo Clinic’s Regenerative Neurobiology Laboratory in Rochester, Minnesota. “However, as we know from model systems such as Caenorhabditis elegans, Drosophila and zebrafish, we can learn a great deal from these simpler organisms.”

Transdifferentiation – getting cells of one type to turn into another – is one of the big challenges for regenerative medicine, says Charles ffrench-Constant of the University of Edinburgh, UK. People have long searched for examples of this happening naturally in vertebrates, but to no avail, he says. John Gurdon at the University of Cambridge and Shinya Yamanaka of Kyoto University in Japan won a Nobel prize for forcing human skin cells to turn back into embryonic stem cells in the lab, but – unlike crayfish – this doesn’t seem to be something we are able to do naturally.

What the study appears to show is a remarkable case of this happening naturally in an invertebrate. If its claims hold, and future studies reveal how crayfish blood cells are reprogrammed to be neurons, it could offer new therapeutic ways of doing the same with human cells.

“This could be another example of nature finding a way of doing something that we have to do by laboratory manipulations,” says ffrench-Constant. “If one could identify the mechanism, it might point us in the direction of new, better therapies.”